Article
- The EMBO Journal (2004) 23, 3995 - 4006
- doi:10.1038/sj.emboj.7600392
Published online: 23 September 2004
Subject Categories:
PIKE/nuclear PI 3-kinase signaling mediates the antiapoptotic actions of NGF in the nucleus
Jee-Yin Ahn1, Rong Rong1, Xuesong Liu2 and Keqiang Ye1
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, USA
- Cancer Research, DEPT R47S, Abbott Park, USA
Correspondence to:
Keqiang Ye, Emory University School of Medicine, Department of Pathology and Laboratory Medicine, Room 145, Whitehead Building, 615 Michael Street, Atlanta, GA 30322, USA. Tel.: +1 404 712 2814; Fax: +1 404 712 2979; E-mail: kye@emory.edu
Received 22 April 2004; Accepted 11 August 2004
Abstract
PI 3-kinase (PI3K) occurs in the nuclei of a broad range of cell types, and various stimuli elicit PI3K nuclear translocation. However, little is known about the biological function of nuclear PI3K. Here we show that nuclear PI3K and its upstream regulator PIKE mediate the antiapoptotic activity of nerve growth factor (NGF) in the isolated nuclei. The nuclei from NGF-treated PC12 cells, EGF-treated HEK293 cells and HeLa cells are resistant to DNA fragmentation initiated by activated cell-free apoptosome. Nuclei from constitutively active PI3K adenovirus-infected cells display the same resistance as those treated by NGF, whereas PI3K inhibitors, dominant-negative PI3K or PIKE abolishes it. Knockdown of either PI3K or PIKE diminishes the antiapoptotic activity of NGF. PI (3,4,5)P3 alone mimics the antiapoptotic activity of NGF, for which nuclear Akt is required. These results demonstrate that PIKE/nuclear PI3K signaling through nuclear PI (3,4,5)P3 and Akt plays an essential role in promoting cell survival.
Keywords:
- apoptosis,
- DNA fragmentation,
- NGF,
- nuclear PI 3-kinase,
- PIKE
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